Fig. 5.

Protein degradation regulates the efficacy of targeted therapy and chemotherapy. SOCS5, CGRRF1, and Cbl-b promote ubiquitination and subsequent endocytosis of the EGFR, while UPS22, STAMBP, UCHL1, and OTUD7B deubiquitinate EGFR. E3 ligases FBXW7 and RNF149 facilitate ubiquitination of BRAF. USP28 regulates the stability of BRAF by deubiquitinating FBXW7. ANAPC2, β-TrCP, and LZTR1/CUL3 complexes promote KRAS ubiquitination for degradation. E3 ligase TRIM15 and CYLD regulate the ubiquitination and deubiquitylation of ERK, respectively. E3 ligase MAGI3 and FBW7α facilitate the ubiquitination of c-Myc, and USP22, USP28, and OTUD6A stabilize c-Myc. Anti-apoptosis protein FLIP can be stabilized through USP2-mediated deubiquitylation. BCL-2 is ubiquitinated by AMFR and CHIP. MCL-1 can be ubiquitinated by HUWEI and deubiquitylated by USP9X, USP13, or USP17